HLA class I antigen processing machinery (APM) component expression and PD-1:PD-L1 pathway activation in HIV-infected head and neck cancers

• Authors: Sara I. Pai, Harvard University; J. Jack Lee, University of Texas MD Anderson Cancer Center; Thomas E. Carey, University of Michigan; William H. Westra, Johns Hopkins University; Soldano Ferrone, Harvard University; Charles Moore, Emory University; Marina Mosunjac, Emory University; Dong Shin, Emory University; Robert L. Ferris, University of Pittsburgh
• Journal Title: Oral Oncology
• Volume: Volume 77
• Publisher: Elsevier: 12 months | 2018-02-01, Pages 92-97
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.oraloncology.2017.12.014
• Subjects: Health Sciences, Oncology; Health Sciences, Dentistry; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Dentistry, Oral Surgery & Medicine; Human immunodeficiency virus; Human Papillomavirus; Head and neck cancer; PD-1; PD-L1; Immune checkpoint blockade; Antigen processing machinery; SQUAMOUS-CELL CARCINOMA; EMBEDDED TISSUE-SECTIONS; MONOCLONAL-ANTIBODIES; RISK; IMMUNODEFICIENCY; SMOKING; RECURRENT; TRENDS; COHORT; AIDS

Abstract

Human immunodeficiency virus (HIV)-infected individuals are at increased risk for developing several non-AIDS related malignancies and are often excluded from cancer immunotherapy regimens. To evaluate the immune competence of this cancer patient population, we evaluated HLA class I antigen presenting machinery (APM) component expression and PD-1:PD-L1 pathway upregulation in HIV(+) and HIV(−) head and neck cancers (HNCs). Sixty-two HIV(+) and 44 matched HIV(−) controls diagnosed with HNC between 1991 and 2011 from five tertiary care referral centers in the United States were identified. HLA class I APM component, PD-1, and PD-L1 expression were analyzed by immunohistochemical staining with monoclonal antibodies (mAbs). Clinical data was abstracted from the medical records. There was no significant difference between the cases and controls in LMP2, TAP1, HLA-A and HLA-B/C, as well as PD-1 and PD-L1 expression. Overall, 62% of all subjects had high PD-1 expression and 82% of the subjects expressed PD-L1 within the tumor microenvironment. LMP2, HLA-A and HLA-B/C expression were significantly associated with moderate to high PD-1 expression in the HIV(+) HNC cases (p =.004, p =.026, and p =.006, respectively) but not in the HIV(−) controls. In addition, HLA-A expression was significantly associated with PD-L1 expression in the HIV(+) HNC cases only (p =.029). HIV-infected individuals diagnosed with HNC do not have any detectable defects in HLA class I APM component expression and in PD-1:PD-L1 pathway activation. Given the current successes of HAART therapy in maintaining immune cell counts, HIV(+) patients diagnosed with cancer may benefit from the recently FDA-approved immune checkpoint blockade therapy.